Risk Factors For Peripheral Arterial Disease Research Articles

Risk factors for at-risk foot and peripheral artery disease among the population with diabetes: A multicommunity-based cross-sectional study

AimsThis study aimed to investigate the prevalence, characteristics, and influence factors of the at-risk foot with diabetes mellitus (DM). MethodsThis study included 3030 DM patients from the at-risk foot screening program of Shanghai in China between March 21 and April 30 in 2021. Data were collected from the questionnaire survey, physical examination, and fasting blood sample. ResultsThe prevalence of at-risk foot was 27.8% among DM patients. After adjusted, the risk of higher at-risk grade increased with age and urinary albumin creatinine ratio (OR = 1.04, 95%CI = 1.02–1.06; OR = 1.001, 95%CI = 1.000–1.002, respectively), whereas decreased with estimated glomerular filtration rate (eGFR) (OR = 0.991, 95%CI = 0.984–0.998). The incidence of peripheral artery disease (PAD) was 11.1% in all people with DM, and age, pulse rate, and low-density lipoprotein were independent risk factors for PAD. In contrast, high-density lipoprotein, eGFR, and lymphocyte-to-monocyte ratio were independent protective factors for PAD. Glycated hemoglobin HbA1c was not an independent risk factor for increased risk grade or more severe PAD. ConclusionsThe at-risk foot accounted for a high percentage among DM patients. Advanced age and renal dysfunction are independent risk factors for the at-risk foot. Glycemic control does not reduce the risk grade of at-risk foot and the incidence of PAD.

Admixture mapping of peripheral artery disease in a Dominican population reveals a putative risk locus on 2q35.

Peripheral artery disease (PAD) is a form of atherosclerotic cardiovascular disease, affecting ∼8 million Americans, and is known to have racial and ethnic disparities. PAD has been reported to have a significantly higher prevalence in African Americans (AAs) compared to non-Hispanic European Americans (EAs). Hispanic/Latinos (HLs) have been reported to have lower or similar rates of PAD compared to EAs, despite having a paradoxically high burden of PAD risk factors; however, recent work suggests prevalence may differ between sub-groups. Here, we examined a large cohort of diverse adults in the BioMe biobank in New York City. We observed the prevalence of PAD at 1.7% in EAs vs. 8.5% and 9.4% in AAs and HLs, respectively, and among HL sub-groups, the prevalence was found at 11.4% and 11.5% in Puerto Rican and Dominican populations, respectively. Follow-up analysis that adjusted for common risk factors demonstrated that Dominicans had the highest increased risk for PAD relative to EAs [OR = 3.15 (95% CI 2.33-4.25), p < 6.44 × 10-14]. To investigate whether genetic factors may explain this increased risk, we performed admixture mapping by testing the association between local ancestry and PAD in Dominican BioMe participants (N = 1,813) separately from European, African, and Native American (NAT) continental ancestry tracts. The top association with PAD was an NAT ancestry tract at chromosome 2q35 [OR = 1.96 (SE = 0.16), p < 2.75 × 10-05) with 22.6% vs. 12.9% PAD prevalence in heterozygous NAT tract carriers versus non-carriers, respectively. Fine-mapping at this locus implicated tag SNP rs78529201 located within a long intergenic non-coding RNA (lincRNA) LINC00607, a gene expression regulator of key genes related to thrombosis and extracellular remodeling of endothelial cells, suggesting a putative link of the 2q35 locus to PAD etiology. Efforts to reproduce the signal in other Hispanic cohorts were unsuccessful. In summary, we showed how leveraging health system data helped understand nuances of PAD risk across HL sub-groups and admixture mapping approaches elucidated a putative risk locus in a Dominican population.

A Pilot Program to Educate High-School Students Regarding Vascular Disease: The Western New York Model

Public education and awareness are critical to addressing issues related to vascular health and disease. However, to date, little work has been done at the community level with regard to outreach to at-risk populations and to address these knowledge gaps. We describe an intervention to educate high-school students regarding vascular disease with aims to improve community knowledge and to also promote further inquiry into the field of vascular surgery. An educational initiative was commenced in three public high schools. A team of vascular surgeons, vascular residents/fellows, medical students, and vascular lab technicians provided in-class education sessions for the length of a class period (approximately 50 minutes). During each session, there was an interactive presentation on risk factors, presentation, and treatment of peripheral arterial disease, stroke, and abdominal aortic aneurysms. This was followed by hands-on stations where students were introduced to endovascular tools and 3D-printed aortic models, as well as a station where students performed ultrasound examinations of their own carotid arteries and abdominal aortas, and ankle brachial indexes were performed. Before and after each session, substantive quizzes regarding vascular disease were administered, and results of the quizzes were tracked. A total of 155 students completed pre-educational session quizzes, and 132 students completed postsession quizzes (Table). Five questions were included on the pre- and postsession quizzes: peripheral arterial disease risk factors (question 1), smoking-related risks (question 2), abdominal aortic aneurysm symptoms (question 3), stroke symptoms (question 4), and smoking pathophysiology (question 5). An improvement was seen in the aggregate number of correct responses for each question (Table). There was also an increase in the total number of students who scored four correct: 7 (4.5%) presession to 20 (15.2%) postsession, and those who scored five correct: 0 (0%) presession to 11 (8.3%) postsession. Targeted programs aimed at high-school students by vascular surgeons, trainees, and staff can provide a sustainable model for public education and awareness of vascular disease that increases knowledge and may also spur interest in vascular surgery. Further work is needed to determine if these interventions can increase knowledge not only in students in the community at large but also in populations at risk surrounding these schools.TablePre- and posteducational session quiz resultsPresession correct responses, No. (%)Postsession correct responses, No. (%)Question 1: risk for developing PAD106 (68.4)101 (76.5)Question2: smoking-related risks59 (38.1)59 (44.7)Question3: most common AAA symptom12 (7.7)45 (34.1)Question 4: signs of stroke33 (21.3)44 (33.3)Question 5: smoking pathophysiology75 (48.4)75 (56.8)Total N = 155Total N = 132Total no. of correct responses 018 (11.6)9 (6.8) 144 (28.4)31 (23.5) 248 (31.0)32 (24.2) 338 (24.5)29 (22.0) 47 (4.5)20 (15.2) 50 (0)11 (8.3)AAA, Abdominal aortic aneurysm; PAD, peripheral arterial disease. Open table in a new tab

Abstract 546: MicroRNA-1282 As A Cis-Antisense Regulator Of Angiogenesis In Diabetic Critical Limb Ischemia

Introduction: Peripheral artery disease (PAD) is an atherosclerotic occlusive disease that leads to reduced blood flow to the lower extremities and endothelial dysfunction. Some patients develop critical limb ischemia (CLI), a severe manifestation of PAD defined as chronic ischemic rest pain with higher risk of amputation. Major risk factors for both PAD and CLI is type 2 diabetes. However, the pathophysiological contribution of microRNAs (miRNAs), in diabetic CLI progression remains poorly elucidated. Methods: By overlapping plasma miRNA sequencing in PAD patients that develop CLI with a mouse model, miRNAs were identified in the progression of diabetic limb ischemia. In this study, we describe miR-1282, a previously uninvestigated miRNA that was the highest upregulated miRNA in high-risk diabetic CLI human subjects. Results: Preliminary studies uncover a mouse ortholog of human miR-1282, a cis-antisense miRNA, that strongly inhibits the expression of SERF2 (small EDRK-rich factor 2), a protein-coding gene located on the opposite DNA strand in both human and mouse endothelial cells. SERF2 is predicted to affect the formation of aggresomes, the inclusion bodies of misfolded proteins; however, its molecular function is also poorly understood. MiR-1282 expression was decreased by diabetic stimuli such as hypoxia and glucose; and its expression inversely correlated with SERF2 expression in endothelial cells. Our in vitro studies indicate that miR-1282 mimic overexpression or SERF2 siRNA-mediated inhibition reduced a range of endothelial angiogenic assays and inhibits apoptosis. Proteomics by tandem mass-tag mass-spectrometry and transcriptomics by RNA-Seq suggest that miR-1282 likely regulates protein quality control system (SERF2, BAG1, BAG3, and HSPB8) and regulated cell death (CASP3, SLC7A11, and CTH), among others. Intriguingly, intramuscular administration of miR-1282 significantly improved blood flow recovery by laser doppler imaging in the hindlimbs of diabetic db/db mice compared to control injected mice. Conclusion: Taken together, the cis-antisense regulatory network of miR-1282-SERF2 axis reveals novel insights in the progression of diabetic CLI.

A modern day perspective on smoking in peripheral artery disease.

Peripheral artery disease (PAD) is associated with increased risk of cardiovascular morbidity and mortality, poor functional status, and lower quality of life. Cigarette smoking is a major preventable risk factor for PAD and is strongly associated with a higher risk of disease progression, worse post-procedural outcomes, and increased healthcare utilization. The arterial narrowing due to atherosclerotic lesions in PAD leads to decreased perfusion to the limbs and can ultimately cause arterial obstruction and limb ischemia. Endothelial cell dysfunction, oxidative stress, inflammation, and arterial stiffness are among the key events during the development of atherogenesis. In this review, we discuss the benefits of smoking cessation among patients with PAD and the use of smoking cessation methods including pharmacological treatment. Given that smoking cessation interventions remain underutilized, we highlight the importance of incorporating smoking cessation treatments as part of the medical management of patients with PAD. Regulatory approaches to reduce the uptake of tobacco product use and support smoking cessation have the potential to reduce the burden of PAD.

Rapamycin restores peripheral blood flow in aged mice and in mouse models of atherosclerosis and Alzheimer's disease.

Peripheral artery disease (PAD), defined as reduced blood flow to the lower limbs, is a serious disorder that can lead to loss of function in the lower extremities and even loss of limbs. One of the main risk factors for PAD is age, with up to 25% of adults over the age of 55 and up to 40% over the age of 80 presenting with some form of the disease. While age is the largest risk factor for PAD, other risk factors include atherosclerosis, smoking, hypertension, and diabetes. Furthermore, previous studies have suggested that the incidence of PAD is significantly increased in patients with Alzheimer's disease (AD). Attenuation of mTOR with rapamycin significantly improves cerebral blood flow and heart function in aged rodents as well as in mouse models of atherosclerosis, atherosclerosis-driven cognitive impairment, and AD. In this study, we show that rapamycin treatment improves peripheral blood flow in aged mice and in mouse models of atherosclerosis and AD. Inhibition of mTOR with rapamycin ameliorates deficits in baseline hind paw perfusion in aged mice and restores levels of blood flow to levels indistinguishable from those of young controls. Furthermore, rapamycin treatment ameliorates peripheral blood flow deficits in mouse models of atherosclerosis and AD. These data indicate that mTOR is causally involved in the reduction of blood flow to lower limbs associated with aging, atherosclerosis, and AD-like progression in model mice. Rapamycin or other mTOR inhibitors may have potential as interventions to treat peripheral artery disease and other peripheral circulation-related conditions.

A clinico-radiological study of Peripheral Arterial Disease in patients with type 2 Diabetes Mellitus using ankle-brachial index and peripheral arterial doppler

Background: Peripheral Arterial Disease (PAD) is an important complication of Diabetes Mellitus (DM). PAD is a part of systemic illness caused by atherosclerosis, resulting in arterial narrowing. Hence PAD is a marker of atherosclerosis in other parts of the vascular system, especially in the arteries supplying the brain and heart. Over two - third of the patients with PAD are asymptomatic, resulting in inadequate treatment of their risk factors. There is a need to screen every DM patient for effective treatment of PAD and the risk factors. Ankle-brachial Index (ABI) is a useful test for the same. Objective: The objective of the study was to find out the incidence of PAD in DM and the factors affecting it. Materials and Methods: It was a hospital-based prospective observational study. In all, 200 diabetic patients from tertiary care hospital (outpatient and indoor) were screened for PAD using ABI, and those showing ABI &lt; 0.9 were further confirmed using Duplex Ultrasonography (DUS). Smokers and patients with a previous history of lower limb surgery, vasculopathy, or trauma were excluded from the study. Factors affecting the incidence of PAD were also studied. Results: Overall incidence of PAD was 10% using ABI as a screening test, confirmed with DUS. Male gender, aging, obesity, duration of DM, poor control of DM, hypertension, coronary artery disease, cerebrovascular disease, hyperlipidemia, and presence of retinopathy were found to be adversely affecting risk factors for PAD. Conclusion: ABI is a bedside, simple, reliable, non-invasive, and cost-effective clinical test for diagnosing PAD, a marker of atherosclerosis in the body. There is a need to screen for PAD, even in asymptomatic patients, for its early detection and management of risk factors.

Association between lipoprotein(a) and peripheral arterial disease in coronary artery bypass grafting patients.

Peripheral arterial disease (PAD) affects a large population and is associated with various adverse clinical outcomes. Lipoprotein(a) has proatherogenic properties and is associated with PAD incidence and severity. The aim of this study is to explore the association betweenLP(a) and PAD in coronary artery bypass grafting (CABG) patients. A total of 1001 patients were included and divided into two groups: low Lp(a) group [LP(a) < 30 mg/dL] and high Lp(a) group [LP(a) ≥ 30 mg/dL]. A comparison of PAD incidencediagnosed by ultrasoundwas made between the groups. Multivariate logistic regression was conducted to explore the risk factors for PAD. During the analysis,the influence of diabetes mellitus (DM) and gender on LP(a) serum level was taken into consideration. DM history (odds ratio [OR], 2.330, p = .000 for males; OR, 2.499, p = .002 for females) and age (OR, 1.101, p = .000 for males; OR, 1.071, p = .001 for females) were risk factors for PAD. LP(a) ≥ 30 mg/dL was a risk factor for PAD only in female patients (OR, 2.589, p = .003), while smoking history was a risk factor only in male patients (OR, 1.928, p = .000). LP(a) level was not associated with PAD severity inDM patients of both gender. As for female patients without DM, PAD was more severe in the high LP(a) group. In CABG patients,DM history and age were risk factors for PAD. But a high level of LP(a) was a significant risk factor only in female patients. In addition, we are the first to propose a gender deviation in the correlation betweenLP(a) serum level and severity of PAD diagnosed by ultrasound.

Evaluation of Lower Extremity Calcium Score as a Measure of Peripheral Arterial Disease Burden and Amputation Risk

The ankle-brachial pressure index (ABI) and toe-brachial pressure index (TBI) are commonly used diagnostic tools for peripheral artery disease (PAD) that are unreliable in the presence of calcified vessels. In this study, we aimed to demonstrate the utility of the lower extremity calcium score (LECS) in addition to ABI and TBI in measuring disease burden and predicting the risk of amputation in patients with PAD. Patients who were evaluated in the vascular surgery clinic at Emory University for PAD and who underwent noncontrast computed tomography of the aorta and lower extremities were included in the study. Aortoiliac, femoral-popliteal, and tibial calcium scores were measured using the Agatston method. ABI and TBI that were obtained within 6months of the computed tomography scan were noted and divided into categories of PAD severity. Associations between ABI, TBI, and LECS of each anatomic segment were evaluated. Univariate and multivariate ordinal regression analyses were performed to predict the outcome of amputation. Receiver operating characteristic analysis was performed to compare LECS with other variables in its ability to predict amputation. Fifty patients included in the study cohort were divided into LECS quartiles, with 12-13 patients in each quartile. The highest quartile tended to be older (P=0.016), had a higher percentage of diabetics (P=0.034), and had a higher frequency of major amputations (P=0.004) compared to the other quartiles. Patients in the highest quartile of tibial calcium score were more likely to have stage 3 chronic kidney disease (CKD) or greater (P=0.011) and also had a higher frequency of amputation (P<0.005) and mortality (P=0.041). We found no significant association between each anatomic LECS and ABI/TBI categories. On univariate analysis, CKD (Odds Ratio [OR] 12.92 (95% CI 2.01 to 82.83), P=0.007), diabetes mellitus (OR 5.47 (95% CI 1.27 to 23.64), P=0.023), tibial calcium score (OR 6.62 (95% CI 1.79 to 24.54), P=0.005), and total bilateral calcium score (OR 6.32 (95% CI 1.18 to 33.78), P=0.031) were associated with increased risk of amputation. On multivariate stepwise ordinal regression, TBI and tibial calcium score were identified as important predictors of amputation, with hyperlipidemia and CKD increasing the overall prediction of the model. On Receiver operating characteristic analysis, the addition of the tibial calcium score (area under the curve 0.94, standard error 0.048) significantly improved the prediction of amputation compared to hyperlipidemia, CKD, and TBI alone (area under the curve 0.82, standard error 0.071, P=0.022). The addition of tibial calcium score to other known PAD risk factors may improve the prediction of amputation in patients with PAD.

Lower-limb peripheral arterial disease and amputations in people with diabetes: Risk factors, prognostic value and management

Lower-limb peripheral arterial disease (PAD), is a common manifestation of systemic atherosclerosis, resulting from a partial or complete obstruction of at least one lower-limb arteries. PAD is a major endemic disease with an excess risk of major cardiovascular events and death. It also leads to disability, high rates of lower-limb adverse events and non-traumatic amputation. In patients with diabetes, PAD is particularly frequent and has a worse prognosis than in patients without diabetes. The risk factors of PAD are comparable to those for cardiovascular disease. The ankle-brachial index is usually recommended to screen PAD despite its limited performance in patients with diabetes, affected by the presence of peripheral neuropathy, medial arterial calcification, incompressible arteries and infection. Toe brachial index and toe pressure emerge as alternative screening tools. The management of PAD requires strict control of cardiovascular risk factors including diabetes, hypertension and dyslipidaemia, the use of antiplatelet agents and lifestyle management, to reduce cardiovascular adverse events, but few randomized controlled trials have evaluated the benefits of these treatments in PAD. Several advances have been achieved in endovascular and surgical revascularization procedures, with obvious improvement in PAD prognosis. Further studies are required to increase our understanding of the pathophysiology of PAD and to evaluate the interest of different therapeutic strategies in the occurrence and progression of PAD in patients with diabetes. Here, we present a narrative and contemporary review to synthesize the key epidemiology findings, screening and diagnosis methods, and major therapeutic advances regarding PAD in patients with diabetes.

The Link Between Reproductive History, Cardiovascular Disease, and Peripheral Arterial Disease in Women: Implications for Practice

The average life expectancy in the United States fell for the second straight year. Attributed mostly to COVID-19 and unintentional injuries (driven by drug overdoses), the third most prevalent cause of death is heart disease. Peripheral arterial disease (PAD) is an often-unrecognized global pandemic affecting more than 220 million. Since early 2000, the incidence of PAD has increased by 25% globally, Once considered a male-dominated disease, PAD is a significant cause of morbidity and mortality among women. This article provides a comprehensive review of the sex-linked risk factors for PAD that pose additional threats for women. Implications for practice are provided.

S-07-5: ASPROSIN INDUCES VASCULAR ENDOTHELIAL- TO-MESENCHYMAL TRANSITION IN DIABETIC LOWER EXTREMITY PERIPHERAL ARTERY DISEASE

Objective: Altered adipokine secretion in dysfunctional adipose tissue facilitates the development of atherosclerotic diseases including lower extremity peripheral artery disease (PAD). Asprosin is a recently identified adipokine and displays potent regulatory role in metabolism, but the relationship between asprosin and lower extremity PAD remains uninvestigated. In this study, we investigated the effect of asprosin accounting for the lower extremity vascular injury in diabetic patients based on the metabolic profiles of PAD. Design and method: 33 type 2 diabetes mellitus (T2DM) patients (DM), 51 T2DM patients with PAD (DM+PAD) and 30 healthy normal control (NC) volunteers were recruited and the blood samples were collected for detecting the circulatory asprosin level and metabolomic screening. RNA sequencing was performed using the aorta tissues from the type 2 diabetic db/db mice and its control db/m mice. Moreover, human umbilical vein endothelial cells (HUVECs) were treated with asprosin to determine its impact on the endothelial-to-mesenchymal transition (EndMT). Results: The circulating levels of asprosin in DM+PAD group were significantly higher than that of NC group and the DM group. Circulating asprosin level was remarkably negatively correlated with ankle-brachial index (ABI), even after adjusting for age, sex, body mass index (BMI) and other traditional risk factors of PAD (P = 0.049). Logistic regression analysis revealed that asprosin is an independent risk factor for PAD (OR:3.944, 95%CI:1.656 − 9.393, P = 0.002) and receiver-operator characteristic (ROC) curve determined a cut-off value at 188.70 ng/ml with a good sensitivity (74.5%) and specificity (74.6%) of asprosin to distinguish PAD (Area under curve:0.788, 95%CI:0.694 − 0.863, P &lt; 0.001). Data from metabolomics displayed a typical characteristics of de novo amino acid synthesis in collagen protein production by myofibroblasts in which TGF-beta signaling pathway might plays a critical role in patients with PAD. In addition, activation of TGF-beta signaling pathway also appeared in the aortic tissue of db/db mice, suggesting a causal relationship between TGF-beta signaling pathway and artery injury. Asprosin directly induces EndMT in HUVECs in a TGF-beta-dependent manner as TGF-beta signaling pathway inhibitor SB431542 erased the promotional effect of asprosin on EndMT. Conclusions: Elevated circulatory asprosin level is an independent risk factor of lower extremity PAD and might serve as a diagnostic marker. Mechanistically, asprosin directly induces EndMT that participates in vascular injury via activation of TGF-beta signaling pathway.

Outcomes of Vascular Intervention in Diabetic Patients with Peripheral Arterial Disease

BACKGROUND: Peripheral arterial disease (PAD) is more prevalent and often presents as more severe in patients with diabetes mellitus (DM) compared with those without DM. Although some patients may be asymptomatic, symptoms ranging from exertional leg heaviness and fatigue to acute limb loss are possible. PAD has significant physical and psychiatric health consequences, thus management with medical therapy and lifestyle changes are indicated. However, peripheral vascular intervention (PVI) is an increasingly popular method used in patients failing conservative management. The association of PVI with health status in diabetic patients has yet to be determined.&#x0D; &#x0D; METHODS: We analyzed the clinical response to PVI in DM (n=203, 52%) compared with non-DM patients (n=183, 48%), using the Peripheral Arterial Questionnaire (PAQ) for patients during baseline and a maximum 6 months after PVI. 502 patients participated with an exclusion of 116 patients from our analysis due to progression of acute limb ischemia and incomplete data collection. Our finalized study population comprised 386 consecutive patients with symptomatic PAD who had also received PVI treatment during the aforementioned time frame. Our patient population received PVI treatment in the year 2012 at the St. John Hospital and Medical Center in Detroit, MI. We used the PAQ summary score, which summarizes the patients’ level of physical and social function, patient symptoms, and overall quality of life before and after the procedure. This represented the PAD-related Quality of Health (QOH). Our score range is between 0 (lowest health quality) and 100 (highest health quality). &#x0D; &#x0D; RESULTS: Compared with non-DM patients, those with DM were more likely to have a history of prior PVI, an increased prevalence of PAD risk factors, and significantly lower QOH scores at baseline (32.7 +/- 20 vs 37.5 +/- 20.6, p=0.02). After adjustment for baseline confounding, neither the baseline, the change, nor the final summary scores were significantly different between groups. This suggests similar symptomatic and functional improvement in non-DM and DM patients post-PVI. &#x0D; &#x0D; CONCLUSIONS: Following PVI, PAD-specific health status showed a similar improvement in patients with and without DM, illustrating that use of this strategy among patients with multiple comorbidities or diffuse PAD as useful. &#x0D; &#x0D; Key Words: peripheral arterial disease, peripheral vascular intervention, diabetes mellitus, quality of life &#x0D; &#x0D; Figure or Table: &#x0D; Table 5. Comparison of the Summary Score of 6 PAQ Domains Using Median Scores from Mann Whitney U Test of DM and Non-DM Patients in Detroit, MI, USA&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; PAQ domain&#x0D; &#x0D; &#x0D; DM&#x0D; &#x0D; &#x0D; Non-DM&#x0D; &#x0D; &#x0D; P-Value&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Physical limitation&#x0D; &#x0D; &#x0D; 16.6 (75.4)&#x0D; &#x0D; &#x0D; 25.0 (79.8)&#x0D; &#x0D; &#x0D; 0.06&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Symptoms&#x0D; &#x0D; &#x0D; 23.6 (75.4)&#x0D; &#x0D; &#x0D; 27.7 (79.8)&#x0D; &#x0D; &#x0D; 0.24&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Symptom stability&#x0D; &#x0D; &#x0D; 25.0 (75.4)&#x0D; &#x0D; &#x0D; 25.0 (79.8)&#x0D; &#x0D; &#x0D; 0.28&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Social limitation&#x0D; &#x0D; &#x0D; 16.6 (75.4)&#x0D; &#x0D; &#x0D; 25.0 (79.8)&#x0D; &#x0D; &#x0D; 0.07&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Treatment satisfaction&#x0D; &#x0D; &#x0D; 0.0 (75.4)&#x0D; &#x0D; &#x0D; 0.0 (79.8)&#x0D; &#x0D; &#x0D; 0.42&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Quality of life&#x0D; &#x0D; &#x0D; 16.6 (75.4)&#x0D; &#x0D; &#x0D; 25.0 (79.8)&#x0D; &#x0D; &#x0D; 0.06&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Summary score&#x0D; &#x0D; &#x0D; 18.7 (75.4)&#x0D; &#x0D; &#x0D; 26.0 (79.8)&#x0D; &#x0D; &#x0D; 0.049&#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

Development and validation of a nomogram to predict the risk of peripheral artery disease in patients with type 2 diabetes mellitus.

To develop and validate a nomogram for predicting the risk of peripheral artery disease (PAD) in patients with type 2 diabetes mellitus (T2DM) and assess its clinical application value. Clinical data were retrospectively collected from 474 patients with T2DM at the Air Force Medical Center between January 2019 and April 2022. The patients were divided into training and validation sets using the random number table method in a ratio of 7:3. Multivariate logistic regression analysis was performed to identify the independent risk factors for PAD in patients with T2DM. A nomogram prediction model was developed based on the independent risk factors. The predictive efficacy of the prediction model was evaluated using the consistency index (C-index), area under the curve (AUC), receiver operating characteristic (ROC) curve, Hosmer-Lemeshow (HL) test, and calibration curve analysis. Additionally, decision curve analysis (DCA) was performed to evaluate the prediction model's performance during clinical application. Age, disease duration, blood urea nitrogen (BUN), and hemoglobin (P<0.05) were observed as independent risk factors for PAD in patients with T2DM. The C-index and the AUC were 0.765 (95% CI: 0.711-0.819) and 0.716 (95% CI: 0.619-0.813) for the training and validation sets, respectively, indicating that the model had good discriminatory power. The calibration curves showed good agreement between the predicted and actual probabilities for both the training and validation sets. In addition, the P-values of the HL test for the training and validation sets were 0.205 and 0.414, respectively, indicating that the model was well-calibrated. Finally, the DCA curve indicated that the model had good clinical utility. A simple nomogram based on three independent factors-duration of diabetes, BUN, and hemoglobin levels-may help clinicians predict the risk of developing PAD in patients with T2DM.

The ankle-brachial index for assessing the prevalence of peripheral artery disease and cardiovascular risk in patients with type 2 diabetes mellitus

Background and aimsType 2 diabetes mellitus (T2DM) is an important risk factor for peripheral artery disease (PAD). Ankle-Brachial Index (ABI) was found associated with a higher cardiovascular (CV) risk and mortality. The main goals of this study were to establish the prevalence of PAD in a T2DM population, and assess the relationship between PAD and the CV risk calculated with the CUORE Project score (CPS) (https://www.cuore.iss.it/). The association between the ABI, the main risk factors for PAD and T2DM complications was also investigated. Methods and resultsTwo hundred patients were consecutively enrolled. The prevalence of PAD in this population was 17%. The CV risk tended to be higher (p = 0.0712) in the group with a pathological ABI than in the group with a normal ABI. Glycated hemoglobin (r = −0.1591; p = 0.0244), total cholesterol (r = −0.1958; p = 0.0054), LDL cholesterol (r = −0.1708; p = 0.0156) and systolic blood pressure (r = −0.1523; p = 0.0313) correlated significantly and inversely with the left ABI. The frequency of diabetic retinopathy was significantly higher in the group with a pathological ABI (p = 0.0316). ConclusionsThe data reveal a high prevalence of PAD in patients with T2DM. The CPS confirmed that patients with a pathological ABI have tendency to a higher CV risk. The results point to the importance of an accurate CV assessment – also measuring individuals’ ABI and calculating their CPS - to better pinpoint those at high risk of PAD, especially among patients with T2DM.

Abstract 11460: Sleep Duration, Quality, and Risk of Peripheral Artery Disease: Multinational Cohort and Mendelian Randomization Studies

Introduction: Sleep duration and quality have been linked to atherosclerosis, however the effects on peripheral artery disease (PAD) specifically have not been well characterized. We conducted cohort, case-control, and Mendelian randomization analyses across three large multinational samples (Sweden, United Kingdom, United States) to evaluate associations between sleep traits and risk of PAD. Hypothesis: Abnormal sleep duration and poor sleep quality are associated with increased risk of PAD. Methods: Sleep traits (including duration, subjective quality, daytime napping, snoring, apnea, and insomnia) were assessed for associations with incident PAD using Cox proportional hazards regression within a cohort of 53,416 Swedish adults. Replication was sought in a case-control study of 28,123 PAD cases and 128,459 controls from the VA Million Veteran Program (MVP) and a cohort study of 452,028 individuals from the UK Biobank (UKB). Two-sample Mendelian randomization (MR) was used to estimate causal effects of sleep-related traits on PAD (31,307 PAD cases 211,753 controls). Results: Observational analyses demonstrated a U-shaped association between sleep duration and PAD risk. In Swedish adults, incident PAD risk was higher in those with short sleep (&lt;5 hours; hazard ratio (HR) 1.74; 95% confidence interval (CI) 1.31-2.31) or long sleep (≥8 hours; HR 1.24; 95% CI 1.08-1.43), compared to individuals with a sleep duration of 7 to &lt;8 hours/night. This finding was supported by case-control analysis in MVP and cohort analysis in UKB. Observational analysis also revealed positive associations between poor sleep quality (HR 1.81; 95% CI 1.13-2.90) and daytime napping (HR 1.32; 95% CI 1.18-1.49) with PAD. MR analysis supported an inverse association between sleep duration (odds ratio per hour increase, 0.79, 95% CI, 0.55, 0.89) and PAD, and an association between short sleep and increased PAD (odds ratio, 1.20, 95% CI, 1.04-1.38). MR also found an association between insomnia with PAD (OR 1.10; 95% CI 1.05-1.15) and a reverse association of PAD on shorter sleep (OR 1.05; 95% CI 1.01-1.10). Conclusions: Short sleep duration and measures of poor sleep quality may be causal risk factors for PAD. Maintenance of healthy sleep habits may help prevent PAD.

Management of Peripheral Arterial Disease: Lifestyle Modifications and Medical Therapies.

Peripheral artery disease (PAD) commonly refers to atherosclerotic narrowing of noncoronary arteries, primarily those supplying the lower extremities. The risk factors for PAD include smoking, hyperlipidemia, hypertension, and diabetes mellitus. Patients with PAD are at a heightened risk of major adverse cardiovascular events (including myocardial infarction, stroke, and cardiovascular death) and major adverse limb events (including progressive symptoms or limb ischemia requiring peripheral revascularization, amputation, and acute limb ischemia), highlighting the need for guideline-directed therapies. Lifestyle modifications and medical therapies are utilized to improve function and outcomes in this patient population. Adherence to a healthy diet and smoking cessation are both associated with better outcomes in patients with PAD. Medical therapies targeting axes of risk, including lipid-modifying therapies, antithrombotic therapies, and targeted diabetes therapies, are available to reduce this risk in patients with PAD; however, significant residual risk remains. Unfortunately, despite guideline recommendations and efforts at education, even available medical therapies remain underutilized in patients with PAD. Continued development of novel therapies and efforts to improve the provision of care in patients with PAD are needed.

A Nomogram for Predicting the Risk of Critical Limb Ischemia in Adults with Hypertension: A Retrospective Study.

Peripheral arterial disease (PAD) presenting with underlying hypertension (HTN) poses a higher risk of bilateral lower limb amputation than PAD patients without HTN. While the role of HTN management of PAD patients has received limited attention. We analyzed the clinical characteristics of PAD in adults with HTN and explored risk factors for PAD to construct a nomogram for evaluating critical limb ischemia (CLI) and lesion severity. Between January 2014 and December 2019, we retrospectively evaluated 1886 patients with peripheral artery disease with coexisting HTN. Patients were randomly divided into training (n = 1320, 70%) and validation cohorts (n = 566, 30%), and according to the subjective experience of PAD [Fontaine classification (I-II vs III-IV)], patients were further classified into intermittent claudication (IC) and CLI groups. LASSO regression and multivariate Cox proportional hazard analyses were used to construct a nomogram using variables defined in the training cohort, which was validated in the validation cohort. The evaluation of the predictive discriminative, accuracy and clinical application are further analyzed. In the training cohort, optimal independent factors included age, male sex, body mass index, diabetes mellitus, heart rate, triglyceride, and uric acid (AM-BDHTU), which were included in the nomogram predicting the CLI risk (all P < 0.05). The C-index values for CLI risk in PAD with HTN patients were 0.729 (95% CI: 0.704-0.807) and 0.728 (95% CI: 0.652-0.744) in the training and validation sets, respectively. Calibration curves indicated good consistency between predicted and actual outcomes. DCA confirmed the clinical utility of the diagnostic model. The AM-BDHTU nomogram, constructed and validated using simple to obtain clinical variables, when combined with the Fontaine classification, effectively predicts the risk of CLI among PAD patients with HTN.

Inflammatory and Prothrombotic Biomarkers, DNA Polymorphisms, MicroRNAs and Personalized Medicine for Patients with Peripheral Arterial Disease.

Classical risk factors play a major role in the initiation and development of atherosclerosis. However, the estimation of risk for cardiovascular events based only on risk factors is often insufficient. Efforts have been made to identify biomarkers that indicate ongoing atherosclerosis. Among important circulating biomarkers associated with peripheral arterial disease (PAD) are inflammatory markers which are determined by the expression of different genes and epigenetic processes. Among these proinflammatory molecules, interleukin-6, C-reactive protein, several adhesion molecules, CD40 ligand, osteoprotegerin and others are associated with the presence and progression of PAD. Additionally, several circulating prothrombotic markers have a predictive value in PAD. Genetic polymorphisms significantly, albeit moderately, affect risk factors for PAD via altered lipoprotein metabolism, diabetes, arterial hypertension, smoking, inflammation and thrombosis. However, most of the risk variants for PAD are located in noncoding regions of the genome and their influence on gene expression remains to be explored. MicroRNAs (miRNAs) are single-stranded, noncoding RNAs that modulate gene expression at the post-transcriptional level. Patterns of miRNA expression, to some extent, vary in different atherosclerotic cardiovascular diseases. miRNAs appear to be useful in the detection of PAD and the prediction of progression and revascularization outcomes. In conclusion, taking into account one’s predisposition to PAD, i.e., DNA polymorphisms and miRNAs, together with circulating inflammatory and coagulation markers, holds promise for more accurate prediction models and personalized therapeutic options.

Dietary Risk Factors and Eating Behaviors in Peripheral Arterial Disease (PAD).

Dietary risk factors play a fundamental role in the prevention and progression of atherosclerosis and PAD (Peripheral Arterial Disease). The impact of nutrition, however, defined as the process of taking in food and using it for growth, metabolism and repair, remains undefined with regard to PAD. This article describes the interplay between nutrition and the development/progression of PAD. We reviewed 688 articles, including key articles, narrative and systematic reviews, meta-analyses and clinical studies. We analyzed the interaction between nutrition and PAD predictors, and subsequently created four descriptive tables to summarize the relationship between PAD, dietary risk factors and outcomes. We comprehensively reviewed the role of well-studied diets (Mediterranean, vegetarian/vegan, low-carbohydrate ketogenic and intermittent fasting diet) and prevalent eating behaviors (emotional and binge eating, night eating and sleeping disorders, anorexia, bulimia, skipping meals, home cooking and fast/ultra-processed food consumption) on the traditional risk factors of PAD. Moreover, we analyzed the interplay between PAD and nutritional status, nutrients, dietary patterns and eating habits. Dietary patterns and eating disorders affect the development and progression of PAD, as well as its disabling complications including major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Nutrition and dietary risk factor modification are important targets to reduce the risk of PAD as well as the subsequent development of MACE and MALE.